The objective of this project is to develop software for the analysis of data from large-scale genotyping and sequencing studies, building on the existing software package PLINK and its companion package PLINK/Seq. Designed to manipulate and analyze whole-genome SNP datasets, PLINK has been actively developed for over six years and has a wide base of users, with over 5000 citations in peer-reviewed journals. Over the past years, we have added considerable support for the analysis of large rare variant datasets, primarily focused on whole-exome sequencing studies in PLINK/Seq. In this renewal application, we seek to 1) provide tighter integration between PLINK and PLINK/Seq, aiming to provide a single interface for both genome-wide association and sequencing studies, particularly in the context of large statistically-imputed datasets; 2) enhance the data-integration facilities already present, across different classes of genetic variation as well as large, diverse datasets; 3) provide improved handling of family-based datasets, focused on de novo and inherited variation in (nuclear) family-based association studies; 4) to work on improving performance on very large datasets. Particular attention will be paid to ensure interoperability with other major software, file-formats and resources that are generated by the broader genetics community.